The structural and stereochemical complexities embodied in many biomedically important natural products present a formidable challenge to synthetic organic chemists. Our research program focuses on the development of new concepts and strategies for organic synthesis. Frequently, to execute such strategies, new reactions must be derived via theoretical and/or mechanistic considerations. In the development of such new reactions, the emphasis is on selectivity. Biologically important natural products are used as templates with which to illustrate these new strategies, concepts, and reactions. Central to the synthesis of any organic molecule is the ability to form carbon-carbon bonds. In general terms, the most common methods for carbon-carbon bone formation involve the employment of carbonions. Nonetheless, other methods of bond formation are frequently desirable. Thus, while our research program encompasses several diverse areas, the underlying theme of non-carbanionic carbon-carbon bond formation has been emphasized. The Research Career Development proposal section outlines projects in two major independent research areas. The first section describes the investigation of synthetic and mechanistic aspects of a series of novel substituent-controlled Claisen rearrangements. In addition to permitting facile and stereocontrolled access to a variety of complex systems, the proposed rearrangements will provide unique insights into the fundamental nature of Claisen transition states. The second section describes our continued development of an alternative strategy for the formation of "aldol adducts" via a cycloadditive route. Central to the approach is the latent synthetic equivalence of a Delta 2-isoxazoline to a beta-hydroxy ketone. A variety of new methods for stereocontrolled isoxazoline formation are proposed, and applications for total synthesis are also planned. It is anticipated that this cycloadditive strategy will provide the first powerful and general alternative to the aldol-type reaction. Finally, a third major research thrust, the development and use of novel free radical reactions in organic synthesis is not included in the proposal section. For this reason, the four accompanying papers are concentrated in this single area to illustrate the excellent progress of this program.